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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data

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Cell Cycle Regulation by Alternative Polyadenylation of CCND1

Qiong Wang1, Guopei He1, Mengmeng Hou1

  • 1State Key Laboratory for Biocontrol, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen University, Higher Education Mega Center, Guangzhou, 510006, P. R. China.

Scientific Reports
|May 3, 2018
PubMed

Insights

Alternative polyadenylation (APA) of CCND1 in cancer accelerates cell cycle and proliferation. CRISPR/Cas9 editing of poly(A) signals (PAS) revealed distinct molecular mechanisms for 3'UTR-APA and coding region-APA in cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • Global shortening of 3' untranslated regions (3'UTRs) via alternative polyadenylation (APA) is a hallmark of cancer cells, yet its functional role remains unclear.
  • The proto-oncogene CCND1, regulating cell cycle progression, exhibits a switch to proximal APA sites in cancer, suggesting a link between APA and oncogenesis.

Purpose of the Study:

  • To investigate the biological function of CCND1 APA in cancer.
  • To elucidate the distinct molecular mechanisms underlying 3'UTR-APA and coding region-APA in CCND1 regulation.

Main Methods:

  • Utilized CRISPR/Cas9 gene editing to modify the poly(A) signal (PAS) of the proximal APA site in CCND1, forcing usage of proximal sites.
  • Performed cell cycle profiling and proliferation assays to assess the functional impact of CCND1 APA site usage.

Main Results:

  • Editing CCND1 to favor proximal APA sites accelerated cell cycle progression and enhanced cell proliferation.
  • Demonstrated that 3'UTR-APA and coding region-APA influence CCND1 function through different molecular pathways.
  • Validated CRISPR/Cas9-mediated PAS editing as an effective tool for studying APA functions.

Conclusions:

  • Proximal APA of CCND1 plays a significant role in promoting cancer cell proliferation and cell cycle advancement.
  • CRISPR/Cas9-based PAS editing is a powerful approach for dissecting the functional consequences and molecular mechanisms of APA in disease contexts.
  • Understanding CCND1 APA mechanisms offers potential therapeutic targets for cancer treatment.

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